HKU Dentistry study presents “positive stress

image: Dr. Waruna L. Dissanayaka and his research team believe that these new findings will promote the development of new strategies to enhance the therapeutic potential of dental stem cells.
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Credit: University of Hong Kong

Stress is generally considered a negative phenomenon, but researchers at HKU Dentistry have discovered “positive stress” that can induce good changes in dental stem cells to make them more resistant to injury and disease.

The study, published online in the Journal of Dental Research, is the first to show that the adaptive mechanisms of dental stem cells induced by stress preconditioning can stimulate the regeneration of dental pulp tissue. Researchers have found that oxidative stress caused by a low oxygen environment can trigger a protective response to make dental stem cells less vulnerable to damage.

When a tooth is damaged, either by severe decay or injury, the living tissue inside is exposed to harmful bacteria and vulnerable to infection. Once the dental pulp tissue is completely infected, current treatment options are limited to either removing the diseased pulp and filling the emptied canal with artificial materials such as rubber and cement, or extracting the tooth. When a dental core is filled with artificial inert materials, the pulpless tooth over time dries out, becomes brittle, and more prone to cracking and reinfection. This could eventually lead to the extraction of the tooth and its replacement with a prosthesis.

The research team led by Dr. Waruna Dissanayaka, Assistant Professor of Oral Biosciences, aims to develop an approach to regenerate lost dental pulp that could revitalize the tooth and allow it to function like a normal tooth.

Stem cell therapy has been considered a promising strategy in dental pulp regeneration. However, since the root canal of the tooth is surrounded by hard tooth tissue with limited blood supply, which creates a harsh environment for cells with low oxygen and nutrient content, low cell viability after in vivo transplantation remains a problem. critical challenge for researchers.

The research team developed a preconditioning protocol that genetically modified cells to mimic a state of response to low oxygen conditions to activate a protein that induces adaptive changes in cells.

Dr. Yuanyuan Han, co-investigator of the team, pointed out: “As this protein has been reported to activate several key adaptive mechanisms, we wondered if this phenomenon could be applied to improve cell survival after transplantation. until sufficient blood supply is achieved. »

“In our study, we found that these cells activate a metabolic mechanism to produce energy under low oxygen conditions and scavenge harmful metabolites produced under stressful conditions.” explained Dr. Han.

“Interestingly, we also found that the preconditioned cells significantly improved dental hard tissue formation in the regenerated pulp tissue.” Dr Dissanayaka added.

“Previous research has revealed that our cells possess a number of stress coping mechanisms, which are regulated by several key genes encoded in our DNA that are normally inactive,” Dr. Dissanayaka said. “If we can turn on these genes, the downstream expression of specific proteins can make cells less vulnerable to injury.”

With the help of Dr. Mohamad Koohi-Moghadam, Assistant Professor of Clinical Artificial Intelligence Research, the team investigated which genes are turned on or repressed during preconditioning and are working further to characterize the upregulated downstream proteins that make cells resistant to damage.

“Dental stem cells have an inherent ability to survive stress,” Dr. Dissanayaka pointed out. “Our goal is to find ways to take advantage of this ability and use positive stress to help regenerate dental tissue.”

Dr. Dissanayaka plans to use knowledge of specific genes and proteins responsible for inducing cell survival to identify drugs that can be used in clinical tissue regeneration. He believes that these new findings will promote the development of new strategies to enhance the therapeutic potential of dental stem cells.

The study won the IADR Colgate Research in Prevention Award at the 2022 IADR General Session. This project was funded by the General Research Fund of the Research Grants Council, Hong Kong.

Research Team
Faculty of Dentistry, University of Hong Kong
Principal Investigator: Dr Waruna Dissanayaka, Assistant Professor in Oral Biosciences Co-Investigator:
– Dr. Han Yuanyuan, PhD student in applied oral science and community dental care
– Dr. Koohi-Moghadam, Mohamad, Assistant Research Professor in Clinical Artificial Intelligence
– Dr. Chen Qixin, PhD candidate in Applied Oral Science and Community Dentistry
– Dr. Zhang Lili, PhD candidate in Applied Oral Science and Community Dentistry

Periodontics and Oral Medicine, School of Dentistry, University of Michigan
Co-investigator: Dr. Hitesh Chopra, postdoctoral researcher
Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

Co-investigator: Professor Zhang Jun
Journal article: “HIF-1α Stabilization Boosts Pulp Regeneration by Modulating Cell Metabolism” is published in the Journal of Dental Research: HIF-1α Stabilization Stimulates Pulp Regeneration by Modulating Cellular Metabolism – PubMed (nih.gov)

For media inquiries:
Ms. Melody Tang, Senior Communications Officer, Faculty of Dentistry, HKU,
Tel: 2859 0494 / 9155 0980, Email: [email protected]


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